1. Field of the Invention
The present invention relates to methods for complexing a protein in a dispersed medium, a method for complexing AHF protein in a dispersed medium, an associated protein produced by the methods of complexing a protein in a dispersed medium, and pharmaceutically effective stabilized protein dosages.
2. Description of the Related Art
Advances in protein engineering have led to the large scale production of proteins and peptides for pharmaceutical purposes. However, for many proteins, the preservation of higher order structure, such as secondary, tertiary and quaternary conformation, is necessary to retain activity. The formulation of such suitable protein and peptide based pharmaceuticals is largely an unsolved problem. Proteins undergo physical and chemical instability, and these instabilities present unique difficulties in the production, formulation, and storage of protein pharmaceuticals (Ahern et al., Pharmaceutical Biotechnology, Borchardt, Ed., pp 550, Plenum Press, New York (1992); Balasubramanian et al., Pharmaceutical Research 17:343-349 (2000)). Denaturation, aggregation, and precipitation are frequent manifestations of physical instability.
Other pharmaceutical concerns of the protein products are shorter half-life and immune response following prolonged use of the drug (Ahern et al., Pharmaceutical Biotechnology, Borchardt, Ed., pp 550, Plenum Press, New York (1992)). Delivery vehicles, such as liposomes, have been explored to improve stability, to prolong the circulation time, and to alter the immunogenecity issues (Balasubramanian et al., Pharmaceutical Research 17:343-349 (2000)). It is known that when liposomes are added to proteins, the stability of proteins are improved since liposomes help reduce the amount of aggregation of the protein. However, the liposomes typically complex with only a small percentage of the total protein. Accordingly, the pharmaceutical developments of such delivery vehicles are hampered by poor association with proteins.
Thus, there is a need for suitable protein and peptide based pharmaceuticals having improved stability during processing and storage conditions; increased dosage spacing by increasing bioavailability, thus reducing cost and patient discomfort; easy handling; and improved delivery to the site of vascular damage. The present invention is directed to overcoming these and other deficiencies in the art by providing a methodology to engineer a complex between a protein and a dispersed system based delivery vehicle.